A multicenter trial of the effectiveness of zeta-globin enzyme-linked immunosorbent assay and hemoglobin H inclusion body screening for the detection of alpha0-thalassemia trait.

Routine laboratories use a hemoglobin H (HbH) screen to detect alpha-thalassemia carriers of fatal hemoglobin Bart's hydrops fetalis. This test is laborious and has sensitivity concerns. A commercial zeta-globin enzyme-linked immunosorbent assay (ELISA) is effective in detecting Southeast Asian (SEA) alpha-thalassemia. We present results of a study of the effectiveness of carrier detection of ELISA and a shortened HbH screen compared with gap polymerase chain reaction. ELISA was superior to the HbH screen for the SEA alpha0-thalassemia trait. The ELISA and H screen were equal for detection of all carriers encountered and combined were more effective than either test alone. A positive zeta-globin ELISA result is diagnostic of SEA alpha-thalassemia, and routine use of the zeta-globin ELISA in combination with a shortened HbH screen will improve the efficacy of prenatal screening for carriers of hemoglobin Bart's hydrops fetalis through improved detection and referral for follow-up DNA testing.

Prevalence of thalassemia in patients with microcytosis referred for hemoglobinopathy investigation in Ontario: a prospective cohort study.

In Ontario, Canada, beta-thalassemia is easily detected through measurement of hemoglobin A2, but most laboratories do not do exhaustive DNA investigations for alpha-thalassemia. Therefore, the prevalence of thalassemia in microcytic samples for hemoglobinopathy investigation in Ontario is unknown. To address this, we performed a prospective cohort study in which samples referred for hemoglobinopathy investigation were also evaluated for alpha-thalassemia by DNA testing. Of 800 samples submitted, 664 were evaluable. Of the 664 patients represented, 163 (24.5%) were beta-thalassemia major carriers, 68 (10.2%) were hemoglobin Bart's hydrops fetalis carriers and, in total, 361 (54.4%) had some form of thalassemia. We conclude that microcytosis due to thalassemia is common in Ontario and that major forms of thalassemia, including forms predisposing to hemoglobin Bart's hydrops fetalis and beta-thalassemia major, are frequent. This illustrates the importance of adequate prenatal and laboratory investigation for these abnormalities in Ontario and other similar multiethnic jurisdictions worldwide.